1. Field of the Invention
This invention is generally directed to pharmaceutical formulations with improved physical and chemical characteristics, comprising gabapentin in tablet form for oral administration. The tablet form can be prepared by spray-coating gabapentin with a binder solution and compressing the spray-coated gabapentin into non-friable, stable tablets. This invention is also generally directed to a method of producing pharmaceutical formulations in tablet form which contain large doses of active drug by spray-coating the active drug with a binder solution and compressing the spray-coated active drug into tablets.
2. Description of the Related Art
Prior art methods for improving the compression characteristics of pharmaceutical formulations involve introducing additional excipients, such as microcrystalline cellulose, as compression aids to prevent fracturing of granules and tablets. However, the inclusion of additional excipients can be expensive and time consuming, can effect the stability of the active drug agent, and can increase the size of the tablet.
Other methods for improving the compression characteristics of pharmaceutical formulations include dissolving the active drug in a binder solution to form a drug solution, spray drying the drug solution to form a powder and then compressing the powder into a tablet. This method, however, is inefficient because it requires a large amount of binder solution. Moreover, dissolving the active drug in a solution can cause stability problems, polymorph conversion, and changes in the crystalline structure of the drug.
U.S. Pat. No. 4,874,614 issued to Becker, discloses a method of preventing the fracture of coated drug granules during the compression process by incorporating into a matrix, along with the granules, microcrystalline cellulose in the amount from 10% to 50% by weight of the total matrix.
U.S. Pat. No. 5,725,884, issued to Sherwood et al., discloses the use of a microcrystalline cellulose based excipient comprising microcrystalline cellulose and silicon dioxide to improve the compressibility of the excipient microcrystalline cellulose, not the active drug substance.
U.S. Pat. No. 5,534,551, U.S. Pat. No. 4,533,674, U.S. Pat. No. 4,605,666 and U.S. Pat. No. 4,710,519 all disclose a method of producing a compressible tablet by dissolving the active agent in a solvent and a binder then spray drying the solution to obtain a spray dried powder that is suitable for direct compression.
IE 3089/90 issued to Augart, et. al., discloses a process for stabilizing pharmaceutical compositions containing gabapentin in solid form. The process entails hydrolyzing gabapentin with a semi-concentrated mineral acid and then converting gabapentin into a solid pharmaceutical composition containing hydroxypropyl methylcellulose, polyvinylpyrrolidine, crospovidone, maize starch, cyclodextrin, talcum, co-polymer of dimethylaminomethacrylic acid and/or neutral methacrylic acid ester.
Various patent applications and patents disclosing processes for preparing the gabapentin, and its methods of use are disclosed in PCT 98/28255, U.S. Pat. No. 4,024,175, U.S. Pat. No. 4,087,544, U.S. Pat. No. 5,084,479, U.S. Pat. No. 4,960,931, and U.S. Pat. No. 4,894,476.